Mingyan Wu1, Bing Li2, Qi Guo1, Liyun Xu2, Yuzhen Zou1, Yongjie Zhang1, Mengling Zhan1, Benyong Xu1, Meiping Ye2, Fangyou Yu3, Zhemin Zhang4, Haiqing Chu5. 1. Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Tongji University School of Medicine, Shanghai 200092, China. 2. Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. 3. Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. 4. Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: zhemindoc@163.com. 5. Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China. Electronic address: chu_haiqing@126.com.
Abstract
OBJECTIVES: The aim of this study was to investigate the molecular mechanisms conferring amikacin (AMK) resistance in Mycobacterium abscessus clinical isolates. METHODS: A total of 194M. abscessus clinical isolates were collected from patients with pulmonary disease during the period 2012-2017. AMK susceptibility was determined by the broth microdilution method. Whole-genome data were used for identification of mutations in resistance-associated genes. Quantitative reverse transcription PCR (qRT-PCR) was performed to measure the gene transcriptional level. RESULTS: AMK showed high in vitro killing activity against M. abscessus, with an MIC50 of 8mg/L and an MIC90 of 16mg/L. Five isolates (2.6%) were resistant to AMK (MIC>1024mg/L), of which four (80.0%) harboured a resistance-associated rrs mutation A1408G. qRT-PCR analysis showed that most of the AMK-resistant isolates (4/5; 80.0%) overexpressed the transcriptional regulator gene whiB7 and the multidrug-efflux transporter gene tap. However, overexpression of the aminoglycoside-modifying enzyme gene eis2 was only observed in one (20.0%) AMK-resistant isolate. CONCLUSION: The AMK resistance rate in M. abscessus clinical isolates in this study was low (2.6%). The A1408G mutation in rrs and overexpression of WhiB7 and Tap were the predominant mechanisms of AMK resistance in M. abscessus.
OBJECTIVES: The aim of this study was to investigate the molecular mechanisms conferring amikacin (AMK) resistance in Mycobacterium abscessus clinical isolates. METHODS: A total of 194M. abscessus clinical isolates were collected from patients with pulmonary disease during the period 2012-2017. AMK susceptibility was determined by the broth microdilution method. Whole-genome data were used for identification of mutations in resistance-associated genes. Quantitative reverse transcription PCR (qRT-PCR) was performed to measure the gene transcriptional level. RESULTS: AMK showed high in vitro killing activity against M. abscessus, with an MIC50 of 8mg/L and an MIC90 of 16mg/L. Five isolates (2.6%) were resistant to AMK (MIC>1024mg/L), of which four (80.0%) harboured a resistance-associated rrs mutation A1408G. qRT-PCR analysis showed that most of the AMK-resistant isolates (4/5; 80.0%) overexpressed the transcriptional regulator gene whiB7 and the multidrug-efflux transporter gene tap. However, overexpression of the aminoglycoside-modifying enzyme gene eis2 was only observed in one (20.0%) AMK-resistant isolate. CONCLUSION: The AMK resistance rate in M. abscessus clinical isolates in this study was low (2.6%). The A1408G mutation in rrs and overexpression of WhiB7 and Tap were the predominant mechanisms of AMK resistance in M. abscessus.
Authors: Ka Lip Chew; Sophie Octavia; Roland Jureen; Oon Tek Ng; Kalisvar Marimuthu; Raymond Tzer Pin Lin; Jeanette W P Teo Journal: Microb Genom Date: 2021-11
Authors: Jaycee Cushman; Emma Freeman; Sarah McCallister; Anna Schumann; Keith W Hutchison; Sally D Molloy Journal: BMC Microbiol Date: 2021-06-09 Impact factor: 3.605